Melanin is the natural pigment synthesized in highly specialized cells, melanocytes, present in the skin. The primary function of endogenous melanin is photoprotection of skin and eye tissues against the harmful action of UV light. Overproduction of the melanin pigment occurs in melanoma, a form of skin tumor, while the lack of pigmentation results in a skin disorder called vitiligo. This research project has four main objectives: to study molecular mechanisms of the melanocytotoxic action of phenolic thioether amines (PTEA); to study free radical processes induced by UV irradiation of pheo- and eumelanin pigments and melanogenic compounds cysteinyldopas and hydroxyindoles; to study electron-transfer properties of melanins and melanin precursors; and to study biophysical basis of vitiligo. We found that incubation of depigmenting PTEA agents 4-S-cysteinylphenol (4-S-CP), 4-S-cysteaminylphenol (4-S-CAP), 4-S-homo-cysteaminylphenol (4- S-homo-CAP) and N-acetyl-4-S-cysteaminyl phenol (N-Acetyl-4-S-CAP) in aerated aqueous buffer (pH 6) in the presence of mushroom tyrosinase and metal ions (Mg2+, Zn2+) produced ortho-semiquinone radical/metal ion complexes. In the absence of the metal ions the formation of free radicals was observed only from 4-S-CP and 4-S-CAP. Other PTEA agents afforded weak, melanin-like EPR signals. UV photolysis (>300 nm) of by- products of melanin biosynthesis 5-hydroxy-6-methoxyindole-2-carboxylic acid and 5-methoxy-6-hydroxyindole-2-carboxylic acid in aqueous solutions (pH 10) generated indoloxyl free radicals, hydrogen atoms and/or hydrated electrons. One-electron reduction of arenediazonium cations, acting as electron acceptors, by the melanogenic compounds resulted in the formation of the highly reactive aryl radicals. Because aryl radicals are known to add to adenosine and/or guanosine residues in DNA, this type of reductive activation of diazonium compounds may be related to their mutagenic and carcinogenic activities.